PMID:21474562

Citation	Yim, H, Sung, CK, You, J, Tian, Y and Benjamin, T (2011) Nek1 and TAZ interact to maintain normal levels of polycystin 2. J. Am. Soc. Nephrol. 22:832-7
Abstract	Polycystic kidney disease (PKD) in mice can arise from defects in Nek kinases, which participate in ciliogenesis. PKD can also arise from loss of the protein TAZ, an adaptor protein in the E3 ubiquitin ligase complex that targets the ciliary protein polycystin 2 (PC2) for degradation, but whether Nek and TAZ contribute to the same biochemical pathway is unknown. Here, we report that the nimA-related protein kinase Nek1 phosphorylates TAZ at a site essential for the ubiquitination and proteasomal degradation of PC2. Loss of Nek1 leads to underphosphorylation of TAZ, thereby promoting the abnormal accumulation of PC2. Furthermore, TAZ targets Nek1 for degradation. These data suggest that TAZ and Nek1 constitute a negative feedback loop linked through phosphorylation and ubiquitination and that the interaction of Nek1 and TAZ maintain PC2 at the level needed for proper ciliogenesis.
Links	PubMed PMC3269896 Online version:10.1681/ASN.2010090992
Keywords	Animals; Cell Cycle Proteins/physiology; Cilia/physiology; Mice; Phosphorylation; Polycystic Kidney Diseases/etiology; Protein-Serine-Threonine Kinases/physiology; TRPP Cation Channels/metabolism; Transcription Factors/physiology; Ubiquitination
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Significance

Gene product	Qualifier	GO Term	Evidence Code	Aspect	Notes	Status
MOUSE:NEK1		GO:0006468: protein phosphorylation	ECO:0000315:	P	Figure 1	complete CACAO 5930
MOUSE:WWTR1		GO:0016567: protein ubiquitination	ECO:0000315:	P	Figures 3 and 4	complete CACAO 5933
MOUSE:WWTR1	involved_in	GO:0016567: protein ubiquitination	ECO:0000315: mutant phenotype evidence used in manual assertion	P	Seeded From UniProt	complete

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